Studies of the side chain cleavage of deramciclane in rats with radiolabelled compounds

Kálmán Magyar, József Lengyel, Andrea Bolehovszky, Gyula Grézal, Imre Klebovich

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The pharmacokinetics of deramciclane and especially the fate of its side chain were studied in rats after oral treatment, using 3H- and 14C-labelled (ring- or side chain labelled) deramciclane and 14C-dimethylamino-ethanol (14C-DMAE) radioisomers. The labelled compounds were admixed and the total radioactivities of both labels were simultaneously determined. The data obtained from the analysis of the plasma concentration-time curves revealed that an intensive cleavage (30-40%) of the side chain occurred at the ether bond. The core of deramciclane, carrying the ring label, was almost completely eliminated during 24 h, while the elimination of the side chain was very slow (t1/2 β: 99 h). The side chain residue most probably represents dimethylamino-ethanol, but the presence of dimethylglycine (DMG) cannot be excluded. The AUC0-∞ and the MRT values of DMAE were found to be much higher than those of the parent compound. In addition to the plasma levels, the time related changes of the tissue concentrations of the radioisomers of deramciclane were analysed both in the brain and the hypophysis. The concentration-time curves have shown similar characteristics to those of the plasma, but higher concentrations were reached in both organs (the highest in the hypophysis). It is postulated that the low rate of formation and elimination of the metabolite(s) (DMAE or DMG) indicates that, due to their endogenous nature, they can be incorporated into choline/acetylcholine or protein synthesis.

Original languageEnglish
Pages (from-to)217-223
Number of pages7
JournalEuropean Journal of Pharmaceutical Sciences
Volume15
Issue number2
DOIs
Publication statusPublished - 2002

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Pituitary Gland
Ethanol
Choline
Ether
Radioactivity
Acetylcholine
Pharmacokinetics
deramciclane
Brain
Proteins
dimethylglycine

Keywords

  • Deramciclane
  • Metabolism
  • N-Dimethylamino-ethanol
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Studies of the side chain cleavage of deramciclane in rats with radiolabelled compounds. / Magyar, Kálmán; Lengyel, József; Bolehovszky, Andrea; Grézal, Gyula; Klebovich, Imre.

In: European Journal of Pharmaceutical Sciences, Vol. 15, No. 2, 2002, p. 217-223.

Research output: Contribution to journalArticle

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